The project's long-term objective is to improve myocardial preservation during ischemia. This application is directed to the laboratory study of warm continuous blood cardioplegia (WCBC), a novel method of intraoperative myocardial protection that is being rapidly introduced across North America. Comparisons of the functional and metabolic effects of WCBC to those of hypothermic cardioplegic arrest, the current standard clinical method of myocardial protection, are not available. Using the isolated, supported canine heart, left ventricular performance before and after cardioplegic arrest will be compared and metabolism will be examined before, during and after arrest. Performance will be defined by Emax, isovolumic end-diastolic pressure-volume lines, and the relaxation constant. Metabolism will be defined by phosphorus-31 and proton nuclear magnetic resonance spectroscopy and measurement of myocardial oxygen consumption and lactate extraction. 1) The following hypotheses will be tested: that warm continuous blood cardioplegia is associated with better myocardial metabolic preservation and better functional recovery than a) cold continuous cardioplegia with the same solution or b) cold intermittent oxygenated dilute blood cardioplegia. 2) Ischemic intervals interposed during WCBC are a necessary feature of this method of myocardial protection. the ability of WCBC to modify the deleterious effects of normothermic ischemia will be examined, including whether these can be lessened by altering the duration of WCBC preceding and following an ischemic interval. The need for periods of no-flow ischemia is the strongest argument for hypothermic protection. Brief normothermic ischemia following WCBC is well tolerated because the heart is arrested and spared the deleterious effects of hypothermia. However, as ischemia is prolonged it seems likely that the reduced metabolic rate produced by cooling will give the advantage to hypothermic cardioplegia. This hypothesis will be tested. 3) A brief period of ischemia increases the tolerance to subsequent prolonged ischemia; this effect is called "preconditioning". Whether ischemic preconditioning can be induced in the isolated supported canine heart when beating and when arrested by WCBC will be examined. Metabolism and functional recovery will serve as endpoints. The ability safely to prolong intraoperative myocardial ischemia in the setting of WCBC would be advantageous surgically. It is anticipated that the data will have important health-related implications, since over 200,000 patients undergo open heart surgery each year in the United States alone.